A simple in vitro method of evaluating monoclonal antibody binding to tumor tissue

Conference · Sun Jan 01 04:00:00 EST 1984 · J. Nucl. Med.; (United States)

OSTI ID:6781143

Rusckowski, M; Hnatowich, D J; Doherty, P W; Virzi, F; Bogden, A E

Application of hybridoma technology has resulted in the availability of many monoclonal antibodies (MoAbs) which are potentially useful for in vivo tumor localization in cancer diagnosis and therapy. What is now required is a simple and predictive assay which will select those MoAbs with superior properties for clinical trials. The authors have developed a simple in vitro means of evaluating the relative binding properties of a panel of MoAbs to human tumor tissue. Fresh and frozen surgical explants of human colorectal and breast tumor tissue as 1 mm cubes were incubated in microtiter-plate wells containing media and radio-labelled MoAb. A MoAb specific for carcinoembryonic antigen (anti-CEA) was used as a known colorectal-specific MoAb and an anti-prostatic acid phosphatase MoAb (anti-PAP) was chosen to measure non-specific binding. The MoAbs were coupled with DTPA and labeled with /sup 111/In. Kinetic parameters were measured which define the rate of MoAb uptake and levels of saturation in tissue. In colorectal tumor tissue the anti-CEA:anti-PAP binding ratio was about 10 while in breast tumor tissue this value was obtained by saturating the tumor antigenic sites with excess unlabeled anti-CEA: the levels of binding of specific MoAb was reduced to that of the control MoAb. Equivalent results were obtained with the same tissue which had been stored at -70/sup 0/C for 24 hours. Evaluation of 7 anti-breast and 4 anti-colorectal MoAbs in their respective tumor tissues showed good reproducibility of repeat measurements and 1-15 fold differences in binding between different antibodies in the same tissue. The authors' results suggest that this in vitro assay may help to identify superior MoAb for human trials.

• Research Organization: Univ. of Massachusetts Medical Center, Worcester, MA
• OSTI ID: 6781143
• Report Number(s): CONF-840619-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 25:5
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ANIMAL CELLS
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CARCINOEMBRYONIC ANTIGEN
CHELATING AGENTS
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DIAGNOSTIC USES
DISEASES
DRUGS
DTPA
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HUMAN POPULATIONS
HYBRIDOMAS
IN VITRO
IN VIVO
INDIUM 111
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLING
MAMMARY GLANDS
MEDICINE
MINUTES LIVING RADIOISOTOPES
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
POPULATIONS
RADIOISOTOPES
RADIOLOGY
RADIOPROTECTIVE SUBSTANCES
RADIOTHERAPY
SURGERY
THERAPY
TISSUES
TRACER TECHNIQUES
UPTAKE
USES